Healthy and Unhealthy Food Consumption in Relation to Quality of Life among Finnish Female Municipal Employees: A Cross-Sectional Study.

Aspects of good quality of life (QoL) have been found to motivate people to make lifestyle changes. There is also evidence that certain dietary patterns are associated with QoL. The aim of this work was to examine whether consumption frequencies of healthy and unhealthy food items are associated with QoL in female employees. A cross-sectional study was conducted among 631 Finnish female employees (mean age 49 years, SD = 10) from 10 municipal work units in 2015. Information about the participants was collected by physical examination, laboratory tests, self-administered questionnaires, including the Food Frequency Questionnaire (FFQ), and from medical history. QoL was assessed with the EUROHIS-Quality of Life 8-item index. A significant positive association was seen between consumption frequency of healthy foods and the EUROHIS-QOL mean score (p = 0.002). The association was small but comprehensive, also involving most dimensions of QoL. The consumption frequency of unhealthy foods was not associated with QoL. These findings are relevant when designing diet counselling, since QoL is an outcome that has been found to motivate people to change their health habits. Recommending abundant use of healthy foods could be a simple and convenient way of diet counselling at many health care appointments, where time consuming approaches are difficult to conduct.

The Relationship between Dietary Habits and Work Engagement among Female Finnish Municipal Employees.

BACKGROUND: Work engagement reflects work-related well-being. It is positively associated with health, life satisfaction, work efficiency, income level, and occupational prospects. However, little is known about the relationship between work engagement and diet. METHODS: A cross-sectional study was conducted among female Finnish municipal employees (n = 630) in 2015. Work engagement was assessed using the Utrecht Work Engagement Index. The consumption of healthy and unhealthy food items was determined using a food frequency questionnaire. Sociodemographic factors, health behaviors, depressive and anxiety symptoms were assessed with self-administrated questionnaires. RESULTS: Work engagement had a positive relationship with the daily consumption of healthy food items. This association remained significant even after adjusting for age, education years, financial situation, and physical activity. The frequency of consuming unhealthy food items showed no relationship with work engagement. Anxiety and depressive symptoms decreased linearly with the greater consumption of healthy foods. CONCLUSION: Frequent consumption of healthy food items is associated with higher work engagement, irrespectively of the consumption of unhealthy nutrients. These results encourage health care professionals to recommend healthy food items instead of forbidding unhealthy food, as well as employers to support healthy dietary habits among employees.

The Association between Healthy Diet and Burnout Symptoms among Finnish Municipal Employees.

BACKGROUND: Burnout is an undesirable mental condition, which may have a negative impact on individuals' health and work ability. This study aimed to evaluate the relationship between diet and burnout symptoms among female public sector employees. METHODS: A cross-sectional study was conducted in 2015 among 630 female employees from 10 municipal work units of the city of Pori, Finland. Burnout symptoms were assessed with the Bergen Burnout Indicator (BBI). The consumption of food items was determined using the food frequency questionnaire (FFQ). The main food groups were categorized into healthy and unhealthy foods based on the Nordic Nutrition Recommendations for a healthy and balanced diet. RESULTS: In multivariate linear regression analysis, consumption of healthy food items had an inverse relationship with the severity of burnout symptoms independently of age, education years, physical activity, and depressive symptoms. De-tailed analysis revealed that subjects with lower BBI score consumed more often low-fat dairy produce, vegetables, fruit and berries, vegetable food, and white meat. CONCLUSIONS: Frequent consumption of healthy food items is associated with low level of burnout symptoms. Our results emphasize the importance of diverse and balanced healthy diet to promote work well-being.

Altered regulation of ELAVL1/HuR in HLA-B27-expressing U937 monocytic cells.

OBJECTIVE: To investigate the role of HLA-B27 expression in the regulation of RNA binding protein (RBP) Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) expression in Salmonella-infected or LPS-stimulated human monocytic cells, since HuR is a critical regulator of the post-transcriptional fate of many genes (e.g. TNFα) important in inflammatory response. METHODS: U937 monocytic cells were stably transfected with pSV2neo resistant vector (mock), wild type HLA-B27, or mutated HLA-B27 with amino acid substitutions in the B pocket. Cells were differentiated, infected with Salmonella enteritidis or stimulated with lipopolysaccharide. The expression levels of HuR protein and cleavage products (CP1 and CP2) were detected by Western blotting and flow cytometry. Specific inhibitors were used to study the role of PKR and p38 in HuR expression and generation of CPs. TNFα and IL-10 secretion after p38 and PKR inhibition were measured by ELISA. RESULTS: Full length HuR is overexpressed and HuR cleavage is disturbed in U937 monocytic cells expressing HLA-B27 heavy chains (HC). Increased full length HuR expression, disturbed cleavage and reduced dependence on PKR after infection correlate with the expression of glutamic acid 45 in the B pocket that is linked to the misfolding of HLA-B27. CONCLUSION: Results show that the expression of HLA-B27 HCs modulates the intracellular environment of U937 monocyte/macrophages by altering HuR regulation. This phenomenon is at least partly dependent on the misfolding feature of the B27 molecule. Since HuR is an important regulator of multiple genes involved in inflammatory response observations offer an explanation how HLA-B27 may modulate inflammatory response.

Phosphorylation of STAT-1 serine 727 is prolonged in HLA-B27-expressing human monocytic cells.

A tissue antigen, HLA-B27, is strongly associated with a group of rheumatic diseases called spondyloarthritides. Despite the intensive research, the exact role of HLA-B27 in the pathogenesis of these diseases is still unclear. Here we studied whether HLA-B27 modulates the phosphorylation of signal transducer and activator of transcription 1 (STAT-1) serine 727 residue and the localization of STAT-1 in Salmonella-infected human monocytic cells. In addition, we studied the role of signaling molecule double-stranded RNA activated protein kinase (PKR) in these modulatory effects. U937 human monocytic cell transfectants stably expressing wild type HLA-B27 or mutated HLA-B27 heavy chains with amino acid substitutions in the B pocket were prepared. The PMA-differentiated cells were infected with S. enteritidis. Western blotting was used to detect the phosphorylation of STAT-1, and to visualize the localization of STAT-1 in the cells confocal microscopy was used. Specific inhibitors were employed to study the role of PKR in STAT-1 phosphorylation. We discovered that the phosphorylation of STAT-1 serine 727 is prolonged in cells expressing misfolding forms of HLA-B27 after S. enteritidis infection, whereas in mock cells and in cells expressing mutated, non-misfolding HLA-B27 the phosphorylation of serine 727 is transient. Interestingly, STAT-1 serine 727 phosphorylation is partly dependent on PKR. In addition, more STAT-1 is localized in the nucleus of HLA-B27-expressing cells, even before an external trigger, when compared to mock cells. In conclusion, our results show that the phosphorylation of STAT-1 serine 727 residue is prolonged in HLA-B27-expressing monocyte-macrophage U937 cells after bacterial infection. This is of interest since the phosphorylation of serine 727 on STAT-1 is suggested to contribute to macrophage activation and promote inflammatory responses. Therefore, our results provide a mechanism which explains how the expression of an HLA-B27 molecule can impact the course of Salmonella infection and reactive arthritis.

Enhanced phosphorylation of STAT-1 is dependent on double-stranded RNA-dependent protein kinase signaling in HLA-B27-expressing U937 monocytic cells.

OBJECTIVE: To study the phosphorylation of STAT-1 in HLA-B27-transfected human monocytic cells and the role of the signaling molecules double-stranded RNA-dependent protein kinase (PKR) and p38 in STAT-1 phosphorylation. METHODS: U937 human monocytic cell transfectants stably expressing wild-type HLA-B27 or mutated HLA-B27 heavy chains with amino acid substitutions in the B pocket were prepared. Mock-transfected cells were prepared using the antibiotic resistance vectors (pSV2neo or RSV5neo) alone. Phorbol myristate acetate-differentiated cells were stimulated with lipopolysaccharide (LPS) or infected with Salmonella enteritidis. The phosphorylation and expression levels of STAT-1 protein were detected by Western blotting and flow cytometry. Specific inhibitors were added in cell culture to study the role of PKR and p38 in STAT-1 phosphorylation. RESULTS: STAT-1 was constitutively highly phosphorylated on the tyrosine 701 residue in HLA-B27-positive monocytic cells when compared to control cells, even prior to stimulation with LPS or bacteria. This phenotype was associated with the expression of HLA-B27 heavy chains that misfold. In addition, phosphorylation of STAT-1 was dependent on PKR. CONCLUSION: Our results show that STAT-1 tyrosine 701 is constitutively highly phosphorylated in the HLA-B27-expressing monocyte/macrophage cell line. Since phosphorylation of tyrosine 701 on STAT-1 is sufficient to induce interferon (IFN)-dependent genes, constitutive activity of this phosphorylation site may lead to the overexpression of IFN-dependent genes, as well as other STAT-1-dependent genes, in HLA-B27 monocyte/macrophages. Our results offer a mechanism by which B27 expression alone, without any external trigger, is potentially capable of inducing activation of STAT-1, a critical regulator of the inflammatory response.

TLR2 utilization of Borrelia does not induce p38- and IFN-beta autocrine loop-dependent expression of CD38, resulting in poor migration and weak IL-12 secretion of dendritic cells.

Lyme borreliosis is a tick-borne bacterial infection that in many cases is limited to the skin. However, in some patients the bacterium evades the immune response and disseminates into various organs. Dendritic cells (DCs) are among the first cells to meet invading pathogens in the skin. We have previously shown that CD38, an ectoenzyme involved in the migration of DCs and generally upregulated by microbial stimuli, is not upregulated in Borrelia garinii-stimulated DCs. In this paper, we characterize the cellular events that lead to the absence of CD38 on the DC surface after B. garinii stimulation and investigate the consequences of absent CD38 expression for the migration of DCs in vitro and in vivo. The data show that 1) effective signaling via p38 MAPK (and STAT1 and NF-kappaB) is needed for CD38 expression and 2) TLR2 stimulation, as opposed to TLR4 stimulation, does not induce IFN-beta autocrine loop-dependent expression of CD38 and secretion of IL-12. Further, we show that 3) B. garinii-stimulated DCs do not migrate effectively toward CCL19 and CCL21 and 4) after B. garinii infection of mice, the number of DCs migrating from the infection site to draining lymph nodes is only half that induced by Escherichia coli infection. Our results provide evidence for the first time that different TLR use results in different CD38 expression, which correlates with the migratory potential of DCs.

HLA-B27 and host-pathogen interaction.

HLA-B27 is a risk factor closely associated to spondyloarthropathies (SpA). One form of SpA is reactive arthritis (ReA), which develops as a complication after certain bacterial infections (e.g., Salmonellae, Yersiniae, Shigellae, Campylobacteriae and Chlamydiae). The development of infection-triggered complication is a complex train of events between the triggering bacteria and the host. Since most of the patients suffering from ReA are HLA-B27 positive, it has been proposed that HLA-B27 may modulate the interaction between ReA-triggering bacteria and host cell. Besides antigen presenting function, HLA-B27 displays other unusual properties that might be of importance in the development of ReA. These properties (homodimer formation and misfolding of HLA-B27 heavy chain in the endoplasmic reticulum (ER)) may trigger ER-stress signaling pathways in host cell, which in turn may modulate cell signaling in favor of ReA-triggering bacteria. Here we summarize the observations of HLA-B27 modulating the interaction between ReA-triggering bacteria and host cell and discuss potential mechanisms behind the interaction.

Evidence that the p38 MAP kinase pathway is dysregulated in HLA-B27-expressing human monocytic cells: correlation with HLA-B27 misfolding.

OBJECTIVE: To investigate the cause of the enhanced intracellular replication of Salmonella enteritidis in HLA-B27-transfected U937 human monocytic cells and the contribution of HLA-B27 heavy chain (HC) misfolding. METHODS: U937 monocytic cell transfectants stably expressing pSV2neo resistant vector (mock), wild-type HLA-B27, or mutated HLA-B27 HCs with amino acid substitutions in the B pocket were differentiated, infected with S enteritidis, and treated with signaling pathway inhibitors or specific p38 small interfering RNA (siRNA). The numbers of living intracellular bacteria were determined with the colony-forming unit method. To visualize S enteritidis, the bacteria were transformed with green fluorescent protein, and studied by microscopy. RESULTS: Treatment with the p38 MAPK inhibitors or with p38 siRNA enhanced the replication of S enteritidis in U937 transfectants, whereas the other inhibitors had no effect. In mock-transfected cells and in cells expressing the mutated B27 HCs in which the misfolding had been corrected, p38 inhibitors impaired their ability to resist the replication of bacteria (mock, B27.A2B, B27.E45M, and B27.C67A). In contrast, the number of intracellular bacteria was not significantly increased in p38 inhibitor-treated cells expressing misfolded B27 HCs (B27g, B27cDNA, and B27.H9F). CONCLUSION: Our results show that p38 activity plays a crucial role in controlling intracellular S enteritidis in U937 cells. Enhanced replication of bacteria in B27-expressing cells requires that the HCs contain glutamic acid at position 45 and cysteine at position 67. Furthermore, in transfectants expressing misfolded B27 HCs, p38 inhibition had no significant effect on bacterial replication, suggesting that in these cells, the p38 pathway may not function properly.

Transcriptional response of human dendritic cells to Borrelia garinii--defective CD38 and CCR7 expression detected.

Lyme borreliosis is a disease, which can affect several organs and cause a variety of symptoms. In some patients, the infection may become chronic, even after antibiotic therapy, and cause persisting damage. Dendritic cells (DC) are involved in the initiation of innate and adaptive immune responses. To study interactions between Borrelia garinii (Bg), one of the causative agents of Lyme borreliosis, and human DC, we used a cDNA microarray to compare the Bg-induced DC transcriptional response with the response induced by LPS. The Bg-induced response consisted of a smaller number of genes than the LPS-induced response. The microarray showed that the ectoenzyme CD38, which has an important role in DC chemotaxis and migration to lymph nodes, was strongly up-regulated by LPS but practically not at all by Bg. This finding was confirmed with quantitative RT-PCR and with flow cytometry at the protein level. In addition, RT-PCR showed that CCR7 expression was 11-fold greater in LPS-stimulated than in Bg-stimulated cells. These findings suggest that Bg may affect crucial DC functions by blocking the up-regulation of important molecules in DC migration to lymph nodes, thus affecting further immune responses in Lyme borreliosis infection.

Aetiology and pathogenesis of reactive arthritis: role of non-antigen-presenting effects of HLA-B27.

Spondyloarthropathies are inflammatory diseases closely associated with human leukocyte antigen (HLA)-B27 by unknown mechanisms. One of these diseases is reactive arthritis (ReA), which is typically triggered by Gram-negative bacteria, which have lipopolysaccharide as an integral component of their outer membrane. Several findings in vivo and in vitro obtained from patients with ReA and from different model systems suggest that HLA-B27 modulates the interaction between ReA-triggering bacteria and immune cells by a mechanism unrelated to the antigen presentation function of HLA-B27. In this review we piece together a jigsaw puzzle from the new information obtained from the non-antigen-presenting effects of HLA-B27.

Enhanced intracellular replication of Salmonella enteritidis in HLA-B27-expressing human monocytic cells: dependency on glutamic acid at position 45 in the B pocket of HLA-B27.

OBJECTIVE: To reveal the cause of the impaired elimination of Salmonella enteritidis in HLA-B27-transfected human monocytic cells and to study whether the B pocket of HLA-B27 contributes to these modulatory effects. METHODS: Stable U937 cell transfectants expressing HLA-A2, B27, or different forms of B27 with amino acid substitutions in the B pocket were prepared. Mock-transfected cells were prepared using the antibiotic resistance vector (pSV2neo) alone. Cells were differentiated, infected with S enteritidis, and the number of live intracellular S enteritidis organisms was determined using the colony-forming unit method. To visualize intracellular S enteritidis, the bacteria were transformed with green fluorescent protein (GFP), and studied by confocal microscopy. RESULTS: Cells expressing wild-type HLA-B27 were more permissive of intracellular replication of S enteritidis compared with mock-transfected or A2-transfected controls. Cells expressing B27 with an altered B pocket composition having either 6 amino acid substitutions (B27.A2B; substitutions H9F, T24A, E45M, I66K, C67V, and K70H) or a single substitution (B27.E45M) were no longer permissive of S enteritidis replication. In contrast, cells expressing B27 with the single substitution of F for H at position 9 (B27.H9F) retained their permissiveness. Studies using GFP-transformed S enteritidis confirmed that the increase in the amount of intracellular bacteria in B27-expressing cells was due to replication of the bacteria. CONCLUSION: Our data indicate that HLA-B27 expression modulates the host-microbe interaction that results in an impaired capacity of monocytes to resist intracellular replication of S enteritidis. The phenotype is dependent on glutamic acid at position 45 in the B pocket and, thus, may be due to properties of the B27 heavy chain that are related to this residue. The ability of HLA-B27 to confer susceptibility to Salmonella-triggered reactive arthritis may occur, at least in part, through these modulatory effects.

Non-antigen presenting effects of HLA-B27.

Spondyloarthropathies (SpA) are a group of chronic rheumatic diseases, which show a strong asoociation with human leukocyte antigen (HLA)-B27. Although the association between HLA-B27 and the susceptibility to SpA was discovered thirty years ago, the exact mechanism by which HLA-B27 predisposes to disease development remains unclear. The classical role of MHC class I molecules is to present peptides for CD8+ T cells. Therefore, it has been proposed that the antigen presenting function of HLA-B27 is somehow altered in the patients developing SpA. However, despite extensive research, the attempts to create a comprehensive theory that would explain the role of HLA-B27 as an antigen presenting molecule in the development of SpA have been unsuccessful. Reactive arthritis (ReA) belongs to the group of SpA. It is a joint inflammation developing after certain bacterial infections e.g. Salmonella, Yersinia, and Chlamydia. Several unrelated observations indicate that HLA-B27 modulates the interaction between ReA-triggering bacteria and host cell. These findings suggest that HLA-B27 may possess functions, which are unrelated to antigen presentation. In this paper, we summarize these findings and discuss their potential impact in the development of SpA.

The role of infection in the pathogenesis of spondyloarthropathies with special reference to human leukocyte antigen-B27.

Spondyloarthropathies consist of many inflammatory diseases that are closely associated with human leukocyte antigen (HLA)-B27. One of these diseases is reactive arthritis (ReA), which is a joint inflammation that occurs after infections that are caused by certain gram-negative bacteria. The importance of these infections as causative agents of ReA has been clearly established. It is not clear, however, whether these infections contribute to the development of other forms of spondyloarthropathies. The exact mechanism by which HLA-B27 influences disease susceptibility in spondyloarthropathies remains to be determined. The role of HLA-B27 as an antigen-presenting molecule is certainly important in the pathogenesis of these diseases; however, recent data indicate that this molecule may exhibit other functions unrelated to antigen presentation, which may be important in the pathogenesis of ReA. In this paper, the authors summarize the current knowledge of the role of infection in the spondyloarthropathies.

HLA-B27 modulates nuclear factor kappaB activation in human monocytic cells exposed to lipopolysaccharide.

OBJECTIVE: To study whether HLA-B27 modifies some key factors controlling inflammatory responses on lipopolysaccharide (LPS) stimulation in human monocytic cells. METHODS: U937 human monocytic cells were stably transfected with either HLA-B27 genomic DNA, HLA-B27 complementary DNA, HLA-A2 genomic DNA, or with the resistant vector pSV2neo (mock) alone. The cells were stimulated with LPS. Electrophoretic mobility shift assay was performed to determine nuclear factor kappaB (NF-kappaB) and heat-shock factor 1 activities, Western blotting was performed to detect the expressions of inhibitory kappaBalpha (IkappaBalpha) and heat-shock proteins (HSPs), and enzyme-linked immunosorbent assay was performed to measure tumor necrosis factor alpha (TNFalpha) secretion. RESULTS: The expression of HLA-B27 modulated the response to LPS in U937 human monocytic cells. Stimulation with LPS led to faster degradation of IkappaBalpha regulatory proteins, accompanied by faster and prolonged activation of NF-kappaB in HLA-B27-expressing cells compared with HLA-A2 and mock transfectants. The secretion of TNFalpha upon LPS stimulation correlated well with the activation of NF-kappaB. No activation of the heat-shock response was observed. CONCLUSION: Our data indicate that HLA-B27 has effects on host responses to LPS that are unrelated to antigen presentation. Two crucial events in the development of arthritis, the activation of NF-kappaB and the secretion of TNFalpha, were found to be enhanced in HLA-B27-expressing cells upon LPS stimulation. Because LPS is known to be present in the inflamed joints of patients with reactive arthritis (ReA), the enhanced inflammatory response of HLA-B27-positive cells upon LPS stimulation offers an attractive explanation for the role of HLA-B27 in the development of ReA.